title: Immunomodulatory and anti-fibrotic effects of ganglioside therapy on the cardiac chronic form of experimental Trypanosoma cruzi infection.
abstract: Heart failure and sudden death are the most common causes of death in patients with Chagas' disease. The main drug available for Chagas treatment is benznidazole, which eradicates Trypanosoma cruzi parasites during the acute stage of infection. However, its effectiveness during the chronic phase remains unclear. Ganglioside GM1 administration in chronically infected patients resulted to be an effective treatment for the cardiac manifestations of Chagas' disease. However, the precise mechanisms of GM1-induced improvement during chronic T. cruzi infection still remain unknown. The aim of the present study was to evaluate the potential benefits of ganglioside GM1 treatment during the chronic stage of murine chagasic infection, analyzing its influence on myocardial pathology as well as its immunomodulatory effects. The results obtained showed that GM1 therapy diminished the extent of myocardial fibrosis induced by T. cruzi in chronically infected mice. In addition, GM1 treatment resulted in a significant reduction in the myocardial expression of the fibrogenic cytokine TGF-β as well as the proinflammatory cytokines and chemokines IFN-γ, TNF-α and CCL5/RANTES. Our experimental data indicate that GM1 could be a promising immunomodulatory agent with capacity to limit the inflammatory process leading to myocardial tissue damage in chronic chagasic patients.
authors.affiliation: Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños Dr. Ricardo Gutiérrez, Buenos Aires, Argentina.
authors.forename: Romina Andrea
authors.initials: RA
authors.lastname: Cutrullis
authors.forename: Tomás Javier
authors.initials: TJ
authors.lastname: Poklépovich
authors.forename: Miriam
authors.initials: M
authors.lastname: Postan
authors.forename: Héctor Leon
authors.initials: HL
authors.lastname: Freilij
authors.forename: Patricia Beatriz
authors.initials: PB
authors.lastname: Petray
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D007155:Immunologic Factors; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D005677:G(M1) Ganglioside; D007371:Interferon-gamma